Polymeric microspheres are a well-known tool for studying biological and biochemical systems. They are useful in such applications as affinity chromatography cell labeling, cell separation and diagnostic methods. Polyacrolein microspheres have been found to be particularly useful in such applications because of their stability and ease of derivatization [Margel, S., Beitler, U. and Ofarim, M., J. Cell Science 56:157-175 (1982)].
It is known that microspheres can be prepared from .alpha.,.beta.-ethylenically unsaturated aldehydes by several methods and that the chemical structure of the resultant microspheres depends on the method of preparation. Polyacrolein microspheres may be prepared, for example, by base-catalyzed polymerization of acrolein in the presence of the ionic surfactant PGL-NaHSO.sub.3 [Margel, S. et al., J. Cell Sci. 56:157-175 (1982)]. It is also known that polyacrolein microspheres may be prepared by radiation-initiated polymerization of acrolein in the presence of non-ionic surfactants [Rembaum, A., Yen, R. C. K., Kempner, D. H. and Ugelstad, J., J. Immunol. Methods 52:341-351 (1982); U.S. Pat. No. 4,413,070 (1983); and Margel, S. et al., J. Cell Sci. 56:157-175 (1982)].
The polyacrolein microspheres prepared by base-catalyzed polymerization and those prepared by radiation-initiated polymerization differ from one another in chemical structure presumably because the two methods involve different reaction mechanisms. Larger stable microspheres may be prepared by the base-catalyzed method than by the radiation-initiated method, but the radiation-initiated microspheres contain more free aldehyde groups. Additionally, the two types of polyacrolein microspheres differ from one another both qualitatively and quantitatively with respect to internal crosslinking and hydrophilicity.
Because of the greater concentration of free aldehyde groups on radiation-initiated polyacrolein microspheres, such microspheres may be preferred for certain applications in which a high degree of ligand-binding activity is desired. Widespread use of radiation-initiated polyacrolein microspheres, especially homopolymeric polyacrolein microspheres, however, has been hindered by heretofore unresolved preparative problems, foremost of which is the low yield in which the microspheres are obtained (e.g., 17.6% yield, Rembaum, U.S. Pat. No. 4,413,070, issued Nov. 1, 1983). Moreover, attempts to increase the yield of microspheres by using a higher concentration of monomer or by using a higher dose of radiation result only in intractable agglomeration of the starting materials.
A method has now been unexpectedly discovered for producing homopolymeric polyaldehyde microspheres in significantly improved yield.